Association of CNS demyelination and COVID-19 infection: an updated systematic review

Abstract

Background Since the declaration of COVID-19 pandemic, several case reports of demyelination of both peripheral and central nervous systems have been published. The association between CNS demyelination and viral infection has long been documented, and this link was recently reported following SARS-CoV-2 infection as well. Objectives In this systematic review, we aim to investigate the existing literature on CNS demyelination associated with SARS-CoV-2, and the proposed pathophysiological mechanisms. Methods We conducted a systematic review of articles in PubMed, SCOPUS, EMBASE, Cochrane, Google Scholar and Ovid databases, from 1 January 2020 until June 15, 2021. The following keywords were used: "COVID-19", "SARS-CoV-2", "demyelination", "demyelinating disease", "multiple sclerosis", "neuromyelitis optica", and "transverse myelitis". Results A total of 60 articles were included in the final analysis of this systematic review and included 102 patients: 52 (51%) men and 50 (49%) women, with a median age of 46.5 years. The demyelination mimicked a variety of conditions with a picture of encephalitis/encephalomyelitis being the most common. At the same time other patterns were less frequently reported such as MS, NMOSD and even MOGAD. Longitudinally extensive transverse myelitis (LETM) was the most frequently reported pattern of spinal cord involvement. Conclusion A growing body of literature has shown an association between SARS-CoV-2 infection and the development of different types of CNS demyelination. Although causality cannot readily be inferred, this review may suggest a probable causal relationship, through a para-infectious or post-infectious immune-mediated etiology in COVID-19 patients. This relationship needs to be clarified in future research.

A systematic review of cases of CNS demyelination following COVID-19 vaccination

“…Finally, in a recent review ( Ismail and Salama, 2021 ), 102 cases of CNS demyelination were reported in association with COVID-19 infection, from January 1, 2020, until June 15, 2021, while only 32 cases in association with COVID-19 vaccine were reported in a 10-month period. This is in line with robust evidence in literature, which documents a substantially higher risk of demyelination following infections, compared to the different types of vaccines ( García-Grimshaw et al, 2021 ; De Martino et al, 2013 ).…”

Neuroimaging in patients with COVID-19: a neuroradiology expert group consensus

“…The underlying pathophysiological mechanism remains unknown, but a para-infectious or post-infectious immune-mediated aetiology seems possible [ 78 ].…”

New-onset neuromyelitis optica spectrum disorder in a patient with COVID-19 and chronic Hepatitis B co-infection

“…In a recent systematic review, patients with COVID-19 were found to have various patterns of brain and spinal cord demyelination resembling autoimmune neurologic disorders. ( Ismail and Salama, 2021 Aug 12 )…”

“…( Baig, 2020 Oct 21 , Butowt et al, 2021 ) Substantial evidence suggests COVID-19 causes a “cytokine storm” with proinflammatory cytokines, including IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, and IFN-γ that may cross the blood-brain barrier. ( Ismail and Salama, 2021 Aug 12 ) In this manner, the innate immunity mediators of the CNS such as macrophages, microglia, and astrocytes can be affected. Outside the CNS, hyperactivation of proinflammatory T cells, lymphopenia, decreased activity of regulatory T cells may also lead to antibody-mediated damage to the CNS and PNS.…”